Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To investigate the types, incidences, and clinical characteristics of shock in polytrauma patients at different stages after polytrauma.Methods:A retrospective study was conducted on polytrauma patients admitted to multiple trauma centers from June 2020 to December 2021. The inclusion criteria were patients >18 years old and treated due to polytrauma. Exclusion criteria included an admission time of more than 48 h after trauma, a history of malignancy, or metabolic, consumptive, and immunological diseases. The early stage was defined as the period of ≤48 h after polytrauma, and the middle stage was defined as the period between 48 h and 14 days. The patient’s medical history, clinical manifestations, laboratory tests, imaging examination, injury severity score (ISS), and Glasgow coma scale (GCS) were collected. The types, incidences, and clinical characteristics of shock in different stages after polytrauma were analyzed, according to the diagnostic criteria of each type of shock. The differences between the groups were compared by Student’s t test, χ2 test or Mann-Whitney U test. Results:The incidence of the early and middle stage shock after polytrauma were 73.1% and 36.4%, respectively, with statistically significant difference between stages ( P<0.01). There were significant differences in the incidence of hypovolemic shock (83.6% vs. 28.4%), distributed shock (13.7% vs. 80.9%) and cardiogenic shock (3.5% vs. 6.6%) between stages (all P<0.05). The incidence of obstructive shock (8.4% vs. 9.7%, P>0.05) was similar between stages. The incidence of undifferentiated shock was 1.6% and 1.2%, respectively. There were 9.5% patients with multifactorial shock in the early stage and 14.4% in the middle stage. Totally 7 combinations of multifactorial shock were found in different stages after polytrauma. In the early stage, the combination of HS and DS accounted the highest ratio (42.3%) and followed by HS and OS for 28.8%. In the middle stage, the combination of HS and DS was the most common (48.6%) and followed by DS and OS (24.3%). Conclusions:The incidence of shock in polytrauma patients is high. Different types of shock can occur simultaneously or sequentially. Therefore a comprehensive resuscitation strategy is significant to improve the success rate of treatment.

Natto is a soybean product fermented by natto bacteria. It is rich in a variety of amino acids, vitamins, proteins and active enzymes. It has a number of biological activities, such as thrombolysis, prevention of osteoporosis, antibacterial, anticancer, antioxidant and so on. It is widely used in medicine, health-care food, biocatalysis and other fields. Natto is rich in many pharmacological active substances and has significant medicinal research value. This paper summarizes the pharmacological activities and applications of natto in and outside China, so as to provide references for further research and development of natto.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective: To evaluate the prevalence and characteristics of Jackhammer esophagus (JE). Methods: From December 2015 to December 2018, the clinical data of 20 patients with JE in the People's Hospital of Yuhuan were retrospectively analyzed.The clinical data of JE patients with typical symptoms of proton pump inhibitor reactive gastroesophageal reflux disease (GERD) were evaluated.The differences between JE patients with or without GERD or allergic esophagus were analyzed, which including esophagogastroscopy (EGD), dynamic pH impedance monitoring of proton pump inhibitors and proton pump inhibitor tests. Results: Of 20 patients with JE, the average age was (55.86±3.23) years old, and BMI was (26.10±3.21)kg/m².Among JE patients, 10 cases (50.0%) were GERD positive, 2 cases (10.0%) were acid sensitive esophagus, and 8 cases (40.0%) were GERD negative.There were no statistically significant differences in heartburn (P=0.167), nausea (P=0.250), dysphagia (P=0.714) or non-cardiac chest pain (P=0.906) and their duration (P=0.319) among the three types of patients.It also affected the intake of proton pump inhibitor (P=0.377) and heartburn (P=0.494). The total number of reflux in patients with positive GERD caused by JE proton pump inhibitor was significantly increased (P=0.027). Conclusion JE has a low prevalence rate in patients with typical symptoms of GERD and proton pump inhibitor treatment response.In this study, only nearly half of the people were diagnosed as GERD positive, which indicates that additional objective tests are needed to stratify JE phenotypes.

Objective: To screen and identify serum protein biomarkers for the differential diagnosis between ischemic colitis (IC) and ulcerative colitis (UC) by tandem mass tag (TMT) combined with liquid chromatography/tandem mass spectrometry (LC-MS/MS). Methods: From January 2018 to January 2019, at the First Affiliated Hospital of School of Medicine of Zhejiang University, patients with UC or IC, and health controls, each 10 cases, were enrolled into UC group, IC group and normal control (NC) group, respectively. Fasting serum samples of all the subjects were collected. After removal of high-abundance protein, followed by proteolysis, peptide labeling and fractionating, the samples were then processed by mass spectrometry. The protein with TMT data of three groups was obtained and protein with TMT value 0 were removed. Heat map of protein was constructed. The differential protein was defined as the protein fold change over 1.5 or less than 0.67. The Reactome database was used to cluster the pathways of differential proteins among groups. Statistical methods included t test, hypergeometry test and corrected by BH multiple test. Results: A total of 357 serum proteins were identified by proteomic profiling. There were 27 differential proteins between the IC group and the NC group, including six up-regulated proteins and 21 down-regulated proteins. There were 228 differential proteins between the UC group and the NC group, including 75 up-regulated proteins and 153 down-regulated proteins. There were 49 differential proteins between UC group and IC group, including 22 up-regulated proteins and 27 down-regulated proteins. In the comparison of differential proteins between the NC group, IC group and UC group, only the expression of fibrin 3 was statistically significant (the fold change between UC and NC, between UC and IC, between IC and NC were 0.24, 0.46 and 0.53, respectively; t=-5.089, -7.298 and -3.919, all P<0.01). The results of pathway cluster analysis showed that in the comparison of differential proteins between IC group and NC group, only the platelet degranulation pathway was enriched, and 10 proteins were involved in this pathway (P<0.01). In the comparison of differential proteins between UC group and NC group, there were 58 pathways enriched, of which 38 proteins were involved in the platelet degranulation pathway, 16 proteins were involved in the initial complement trigger pathway, 13 proteins were involved in the complement cascade pathway, and 11 proteins were involved in antibody-mediated complement activation pathway (all P<0.01). In the comparison of differential proteins between UC group and IC group, three different pathways were obtained. Among them, nine proteins were involved in the platelet degranulation pathway, seven proteins were involved in the initial complement trigger pathway, and five proteins were involved in the complement cascade pathway (all P<0.01). Conclusions The difference in serum proteome between IC patients and UC patients was significant, and the differential proteins are mainly involved in platelet activation and complement activation. The candidate proteins identified in this study may be used as biomarkers for the differential diagnosis of UC and IC in the future.

Objective To investigate multiple viral antigens in pediatric patients with respiratory infection in Yangzhou.Methods A total of 17 691 children with respiratory infection admitted in our hospital between January 2011 and December 2011 were tested with direct immunof-luorescence method.A total of 7 kinds of virus antigens were detected,including adenovirus (ADV),respiratory syncytial virus (RSV),parainfluenza virus Ⅰ,Ⅱ,Ⅲ(PIV Ⅰ,Ⅱ,Ⅲ),influenza virus A/B(IFA/B).Its epidemiological characteristics was analyzed.Results There were altogether 1 991 positive cases,the detection rate was 11.25％ (1 991/17 691),in which the proportion of RSV was 60.12％ (1 197/1991),followed by PIV llⅢ 14.27％ (284/1 991),ADV 8.04％ (160/1 991),PIV Ⅰ 5.42％ (108/1 991),IFA5.27％ (105/1 991),IFB 4.07％ (81/1 991),PIVⅡ 2.81％ (56/1 991).There was significant difference between male and female in the detection rate of respiratory virus.Respiratory virus detected rate in 1 month to ＜ 1 year old was 59.81％ (1 191/1 991),single virus detection rate was the highest.The detection rate of virus for positive was the highest in winter,accounting for 51.88％ (1 033/1 991),and the lowest in summer for 10.35％ (206/1 991).Conclusion Respiratory virus infection in Yangzhou is influenced by age,season and gender,with infants and young children aged 1 month to 1 year in high-risk infection,and RSV infection occurs mostly,and the male are most likely to be infected in winter.

Objective To investigate multiple viral antigens in pediatric patients with respiratory infection in Yangzhou.Methods A total of 17 691 children with respiratory infection admitted in our hospital between January 2011 and December 2011 were tested with direct immunof-luorescence method.A total of 7 kinds of virus antigens were detected,including adenovirus (ADV),respiratory syncytial virus (RSV),parainfluenza virus Ⅰ,Ⅱ,Ⅲ(PIV Ⅰ,Ⅱ,Ⅲ),influenza virus A/B(IFA/B).Its epidemiological characteristics was analyzed.Results There were altogether 1 991 positive cases,the detection rate was 11.25％ (1 991/17 691),in which the proportion of RSV was 60.12％ (1 197/1991),followed by PIV llⅢ 14.27％ (284/1 991),ADV 8.04％ (160/1 991),PIV Ⅰ 5.42％ (108/1 991),IFA5.27％ (105/1 991),IFB 4.07％ (81/1 991),PIVⅡ 2.81％ (56/1 991).There was significant difference between male and female in the detection rate of respiratory virus.Respiratory virus detected rate in 1 month to ＜ 1 year old was 59.81％ (1 191/1 991),single virus detection rate was the highest.The detection rate of virus for positive was the highest in winter,accounting for 51.88％ (1 033/1 991),and the lowest in summer for 10.35％ (206/1 991).Conclusion Respiratory virus infection in Yangzhou is influenced by age,season and gender,with infants and young children aged 1 month to 1 year in high-risk infection,and RSV infection occurs mostly,and the male are most likely to be infected in winter.

Objective To explore the diagnostic model and clinical application value of serum proteomic fingerprint in inflammatory bowel disease (IBD) .Methods Serum proteome profiles of 72 IBD patients (54 Crohn′s disease (CD) and 18 ulcerative colitis (UC) and 44 healthy controls were analyzed by the weak cation exchange (WCX) beads combined matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF‐MS ) technique . Among three groups , every two groups were compared .Wilcoxon rank sum test was used to screen out the peaks of difference expressed protein (P<0 .05) .Genetic algorithm combining with support vector machine (SVM ) was utilized to select the best diagnostic model .The predictive effects of this model was evaluated by leave one out method (LOO ) . Results The 10 most discriminating protein peaks were screened out between CD group and healthy control group , between UC group and healthy control group , between CD group and UC group . A diagnostic model established with four protein peaks ,the mass‐to‐charge ratio (M /Z ) of them was 3 275 .29 ,4 963 .91 ,4 980 .53 and 5 336 .90 ,could better distinguish CD and healthy controls .The specificity was 97 .7% ,and the sensitivity was 92 .6% in CD diagnosis .A diagnostic model established with four protein peaks ,the M /Z of them was 2 272 .41 ,2 660 .42 ,3 029 .77 and 5 002 .78 ,could better distinguish UC and healthy controls .The specificity was 100 .0% ,and the sensitivity was 94 .4% .A specificity was 50 .0% and sensitivity was 88 .9% in CD diagnosis with the diagnostic model of six protein peaks and the M /Z of them was 2 082 .63 ,2 210 .64 ,4 039 .02 ,4 298 .30 ,4 978 .03 ,5 002 .22 .Conclusion The diagnostic model of serum difference expressed protein in CD and UC is established by MALDI‐TOF‐MS technique and genetic algorithm combining with SVM ,which has high diagnostic value in IBD .

Objective To explore the correlation of total IgE and childhood atopic dermatitis (AD) in maternal serum and newborn cord blood, as well as its clinical significance of allergen testing. Methods Thirty-five cases diagnosed as AD (AD group) were selected, and other 35 children who were not diagnosed as AD (control group) were randomly selected from a birth cohort established in 2009—2011. The total IgE levels were detected by ELISA in maternal serum and newborn cord blood. The serum specific IgE antibody level was detected by quantitative immunoblotting method. Results The serum total IgE level was significantly higher in mother and newborn cord blood in AD group than that in control group (χ2=16.568 and 14.933, P<0.01). Compared to control group, there was a significantly higher positive rate of mother serum allergen includ?ing dust mites, house dust, ragweed pollen, song kind of pollen, poplar, surname and elm pollen, mould, shrimp, marine fish, in AD group (P<0.05). There was a significantly higher positive rate of artemisia pollen and fungi IgE in newborn cord blood in AD group (P<0.05). Conclusion The increased total IgE in maternal serum may play a predictive effect on infants suf?fering from AD. There is no obvious consistency in allergic state between mothers and infants.